The overall objective of the proposed research is to develop a glucose sensor capable of continuous in vivo measurement of body fluid glucose concentrations in diabetic patients without requiring withdrawl of any body fluids for the glucose assay. The availability of such a sensor would constitute a major breakthrough for the clinical handling and basic investigation of diabetes, and its associated complications. Our collaborative efforts over the past several years have resulted in the initial development and testing of a direct potentiometric method for the in vitro measurement of glucose in buffered solution or in serum, using as the test electrode the enzymes glucose oxidase and catalase or only glucose oxidase immobilized on platinum. This approach has been shown to operate satisfactorily in vitro over a clinically useful range of serum glucose concentrations of 5-150 mg/dl. The specific objectives of the proposed work are to define more clearly the mechanism by which the potentiometric signal is generated, the specificity of the response for glucose and the possibility of extending the range of the electrode to a clinically useful upper limit of at least 400 mg glucose/dl, and those modifications that would make the approach more applicable for eventual in vivo use in humans.